The goal of this section is to elucidate the structural and molecular substrate of the active biomechanical mechanism modulating transduction in the mammalian cochlea. Molecular probes any stains will be used to label and localize specific cytoskeletal elements, calcium, and second messenger components. Selection of these structural elements is based on current hypotheses of cell motility and regulation. Conventional light microscopy, laser scanning confocal microscopy and electron microscopy will allow precise definition of their localization within cells of the organ of Corti. 3-D reconstruction and simultaneous staining of more than one component will help define anatomical relationships between different elements. Since markers are not available to all potential components of the structural and molecular substrate, new probes will be generated by raising and characterizing monoclonal antibodies to inner ear tissues. These will then be used to further define the molecular/structural substrate of cochlear function. The relationship of anatomically defined elements of the molecular substrate to function will be determined in three ways. The first approach is to infer cochlear function based on their functions in other tissues. The second approach is to determine which components of the molecular substrate change (and in what way) with changes in function. Molecular/Structural changes will be examined during the developmental appearance of motility and hearing, after physiological and pharmacological manipulation of OHC motility in the mature cochlea spiral with differences in synaptology and response properties. The final approach is to investigate how auditory function is affected by antibodies binding to specific structural/molecular components. This will be determined in animals with endogenous circulating antibodies as well as in animals in which antibodies are applied to the inner ear.